FDA Reassesses Criteria for Rare Disease Trials and Endpoint Selection
Key Insights
The FDA and Duke-Margolis Institute for Health Policy (search) will hold a public workshop on Sept. 29 on statistical considerations for rare disease clinical investigations.
The hybrid meeting at the National Press Club in Washington, D.C. will examine how study design, conduct and analysis can be tailored without losing scientific rigor.
Rare disease developers face barriers including small eligible populations, rapid progression, pediatric onset and reluctance to accept placebo, prompting FDA acceptance of single-arm studies and surrogate endpoints.
The FDA and the Duke-Margolis Institute for Health Policy (search) will convene a public workshop on Sept. 29 to address how reliable evidence can be generated in rare disease development when patient numbers make conventional clinical trials difficult or impossible. The meeting, titled "RISE to the Challenge: Statistical Considerations for Rare Disease Clinical Investigations," runs from 9 a.m. to 4:30 p.m. ET as a hybrid event at the National Press Club in Washington, D.C.
A draft agenda shows the workshop will examine how researchers can tailor the design, conduct and analysis of studies without sacrificing the scientific rigor needed to determine whether a drug or medical device works. Rare disease developers frequently face practical and ethical barriers to conventional randomized trials: eligible patients may number in the dozens rather than thousands, some diseases progress rapidly, others primarily affect children, and patients and families may resist joining a study if they could receive placebo instead of an experimental treatment.
Those constraints have led the FDA to accept single-arm studies, natural-history comparisons, surrogate endpoints and other unconventional forms of evidence in some rare disease programs, and have fueled long-running debate over whether regulatory flexibility can go too far. Sarepta Therapeutics' Exondys 51 became a defining example after the FDA granted accelerated approval in 2016 for a subset of patients with Duchenne muscular dystrophy (search), a decision based on increased dystrophin (search) production as a surrogate endpoint even though agency reviewers questioned whether the relatively small increase was reasonably likely to predict clinical benefit.